吉非罗齐对临床几种常用口服降糖药的作用

摘要/Abstract

摘要： 药物相互作用,尤其是药代学的相互作用的研究近年来成为热点。吉非罗齐是一个临床常用的降脂药物,而在临床高脂血症合并糖尿病情况较多,所以吉非罗齐与口服降糖药合用后是否有相互作用也应该是临床医生的关注点。本文综述吉非罗齐对临床几种常用口服降糖药的药代学和药效学的影响,及从其机制上予以分析。吉非罗齐通过对CYP2C的抑制作用而明显影响口服降糖药的药代学及药效学,所以在临床上合用时需及时监测血糖的浓度或调整口服降糖药的用量。

关键词: 吉非罗齐, 口服降糖药, CYP2C

Abstract: Drug interactions, particularly the studies of interaction between pharmacokinetics become a hot spot in recent years.Gemfibrozil is a lipid-lowering drugs commonly used in clinical, and there are many opportunities hyperlipidemia be in diabetes clinical situation, so whether there are interactions between gemfibrozil and oral agents should also be the concern of clinicians.We review the effect of Gemfibrozil to the pharmacokinetics and pharmacodynamics of several commonly used oral hypoglycemic drug, and to analyze its mechanism. Gemfibrozil inhibited CYP2C and significant effect the pharmacokinetics and pharmacodynamics of oral hypoglycemic drug, so monitoring the blood glucose concentrations in time or adjust the dosage of oral hypoglycemic agents when they are combined in clinical is necessary.

Key words: Gemfibrozil, Oral hypoglycemic agents, CYP2C , , , ,

中图分类号:

R969

淡海丽, 易飞. 吉非罗齐对临床几种常用口服降糖药的作用[J]. 中国临床药理学与治疗学, 2011, 16(1): 116-120.

DAN Hai-Li, YI Fei. Effects of Gemfibrozil on several commonly used oral hypoglycemic agents[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(1): 116-120.

参考文献

[1] 王宇光,高月.中草药对细胞色素P-450酶调控研究进展[J]. 中草药,2003,34(5):477-479.
[2] Wen X, Wang JS, Backman JT,et al.Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9[J].Drug Metab Dispos,2001,29(11): 1359-1361.
[3] Wang JS, Neuvonen M, Wen X, et al.Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes[J]. Drug Metab Dispos, 2002,30(12): 1352-1356.
[4] Deng LJ, Wang F, Li HD .Effect of gemfibrozil on the pharmacokinetics of pioglitazone[J]. Eur J Clin Pharmacol,2005,61(11): 831-836.
[5] Jaakkola T, Backman JT, Neuvonen M,et al.Effects of gemfibrozil, itraconazole,and their combination on the pharmacokinetics of pioglitazone[J]. Clin Pharmacol Ther,2005,77(5):404-414.
[6] Gan J, Chen W, Shen H, et al. Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism[J]. Br J Clin Pharmacol,2010 ,70(6):870-880.
[7] Niemi M, Backman JT, Granfors M, et al. Gemfibrozil considerably increases the plasma concentrations of rosiglitazone[J]. Diabetologia,2003, 46(10):1319-1323.
[8] Laitila J, Neuvonen PJ, Backman JT. Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors[J]. Basic Clin Pharmacol Toxicol,2006,99(1):44-51.
[9] Baldwin SJ, Clarke SE, Chenery RJ.Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone[J]. Br J Clin Pharmacol,1999,48:424-432.
[10]Wen X,Wang JS, Backman JT, KivistKT, Neuvonen PJ.Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9[J]. Drug Metab Dispos,2001,29(11):1359-1361.
[11]Prueksaritanont T, Richards KM, Qiu Y.Comparative effects of fibrates on drug metabolizing enzymes in human hepatocytes[J]. Pharm Res, 2005,22(1):71-78.
[12]Bidstrup TB, Bjrnsdottir I, Thomsen MS, et al.CYP2C8 and CYP3A4 are the principle enzymes involved in the in vitro biotransformation of the insulin secretagogue repaglinide[J]. Br J Clin Pharmacol,2003,56(3): 305-314.
[13]Weaver ML, Orwig BA, Rodriguez LC, et al. Pharmacokinetics and metabolism of nateglinide in humans[J]. Drug Metab Dispos, 2001, 29(4 Pt 1): 415-421.
[14]Tornio A, Niemi M, Neuvonen M, et al.The effect of gemfibrozil on repaglinide pharmacokinetics persists for at least 12 h after the dose: evidence for mechanism-based inhibition of CYP2C8 in vivo[J]. Clin Pharmacol Ther,2008, 84(3):403-411.
[15]Niemi M, Backman JT, Neuvonen M, et al. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide[J]. Diabetologia,2003,46(3):347-351.
[16]Niemi M, Backman JT, Juntti-Patinen L,et al.Coadministration of gemfibrozil and itraconazole has only a minor effect on the pharmacokinetics of the CYP2C9 and CYP3A4 substrate nateglinide[J].Br J Clin Pharmacol,2005,60(2):208-217.
[17]Backman JT, Honkalammi J, Neuvonen M,et al. CYP2C8 Activity recovers within 96 hours after gemfibrozil dosing: estimation of CYP2C8 half-life using repaglinide as an in vivo probe[J].Drug Metab Dispos,2009,37(12):2359-2366.
[18]Niemi M, Cascorbi I, Timm R,et al. Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes[J]. Clin Pharmacol Ther, 2002,72(3):326-332.
[19]Niemi M, Neuvonen PJ, Kivist KT. Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride[J]. Clin Pharmacol Ther,2001, 70(5):439-445.
[20]Ogilvie BW, Zhang D, Li W, et al. Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions[J]. Drug Metab Dispos,2006,34(1):191-197.
[21]Kalliokoski A, Backman JT, Kurkinen KJ, et al.Effects of gemfibrozil and atorvastatin on the pharmacokinetics of repaglinide in relation to SLCO1B1 polymorphism[J]. Clin Pharmacol Ther,2008, 84(4):488-496.
[22]Gan J, Chen W, Shen H, et al.Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism[J]. Br J Clin Pharmacol, 2010,70(6):870-880.
[23]吴剑琴,杨二杨,官兴荣.吉非罗齐对2 型糖尿病血脂及血糖代谢的影响[J].实用医学杂志,2000,16(5):410-411.
[24]黄燕南.吉非罗齐治疗糖尿病脂代谢异常40 例临床分析[J].现代中西医结合杂志,2005 , 14(3):319.
[25]漆泓,孙明,周宏研.吉非罗齐对代谢综合征血脂及胰岛素抵抗的影响[J].中国现代医学杂志,2004,14(17):50-53.